5HT(1A) RECEPTOR AGONIST DIFFERENTIALLY INCREASES CYCLIC-AMP CONCENTRATION IN INTACT AND LESIONED GOLDFISH RETINA - IN-VITRO INHIBITION OF OUTGROWTH BY FORSKOLIN

5HT(1A) receptors occur in the retina of various species and the admin istration of 5HT(1A) agonists results in the inhibition of outgrowth f rom postcrush goldfish retinal explants. The levels of cyclic AMP (cAM P) play a role in the modulation of the outgrowth of the nervous syste m. Moreover, the stimulation of central 5HT(1A) receptors with the ago nist 8-hydroxy-2-(di-n-propylamino)tetralin has been reported to produ ce an increase or decrease in the activity of adenylate cyclase. In th e present investigation we studied the effect of adenylate cyclase sti mulation by forskolin, as well as the modulatory effects of 5HT(1A) re ceptor agonists and antagonists on the production of cAMP in the goldf ish retina, and on the outgrowth of this tissue in vitro. 8-Hydroxy-2- (di-n-propylamino)tetralin produced a significant and dose-dependent i ncrease in cAMP concentration. This effect was not additive to the sti mulation produced by forskolin. By contrast, as previously described, the 5HT(1A) agonist decreased cAMP concentration in the hippocampus of the rat. Both effects were significantly impaired by the 5HT(1A) anta gonist WAY-100,135. A significant effect of the antagonist alone was o bserved only in the goldfish retina. The increase in cAMP levels was g reater in the intact than in the postcrush retina. In addition, forsko lin decreased the outgrowth of postcrush retinal explants in a dose-de pendent manner, suggesting the importance of critical levels of cAMP i n this process. Taken together, 5HT(1A) receptors seem to be positivel y coupled to adenylate cyclase in the goldfish retina, where cAMP play s a role as a modulator of outgrowth and regeneration. The inhibitory effect of 5HT(1A) receptor agonists on retinal outgrowth might be medi ated through the production of cAMP. The activation of other subtypes of 5HT receptors positively coupled to adenylate cyclase by the 5HT(1A ) agonist, such as 5HT(7), cannot be discarded. Copyright (C) 1996 Els evier Science Ltd